Bridged ring carbazoles



United States Patent 3,337,581 BRIDGED RING CARBAZOLES Guy Robert Collins, Midland, Mich., assignor to The Dow Chemical Company, Midland, Mich., a corporation of Delaware No Drawing. Original application Nov. 29, 1963, Ser. No. 327,040, now Patent No. 3,285,911, dated Nov. 15, 1966. Divided and this application May 4, 1966, Ser. No. 547,427

3 Claims. (Cl. 260-315) This is a division of my copending application Ser. No. 327,040, filed Nov. 29, 1963, now US. Patent No. 3,285,- 91 1. t

This invention relates to a new cyclization reaction of N-sulfinylanilines and to novel chemical compounds which are thereby obtained. It also relates to novel derivatives of these products.

N-sulfinylaromatic amines, which have the general formula Ar-Nfl=O, are known to react With ,3-dienes to produce substituted 1,2-thiazine oxides according to the equation Recently, Beecken and Korte (Tetrahedron 18, 1527 (1962)) described the reaction of N-sulfinylanilines with diphenylketene which involved a 1,2-addition to form a cyclic product. I p

N -Ar N Ar A few other reactions of N-sulfinylanilines involving 12-;

NSO

R i g i have been found to react with the olefinic bond in nor: bornene and certain substituted bicycloheptenes of the formula ace RI/I R l RIII/ wherein R is a substituent which is unreactive under the reaction conditions, for example, hydrogen, lower alkyl, lower alkoxy, phenyl, halogen, or nitro, R" and R' are similarly unreactive substituents and preferably R is hydrogen or methyl and R" is hydrogen, methyl, or cyano, not more than one R" being cyano. Of particular interest arethe reaction products derived from norbornene itself and cyanonorbornene and such products wherein the substituent on the aromatic ring of the sulfinylaniline has been modified by further reaction, for example, by reduction of a nitro substituent to an amino group, or where an alkyl group has been attached to the nitrogen atom. These products are represented by the structural formula:

wherein Y is cyano or hydrogen, R is hydrogen or lower alkyl, and X is hydrogen, lower alkyl, lower alkoxy, phenyl, halogen, N0 or NH By the terms lower alkyl and lower alkoxy are meant groups containing 1-4 carbon atoms such as methyl, ethyl, isopropyl, butyl, methoxy, ethoxy, and butoxy.

The chemical nomenclature used herein is consistent with that employed by Chemical Abstracts. The numbering according to that system of the heterocyclic structures described in this specification is shown below.

1,4-methanocarbazole nucleus The diagrammatic structure 4 the solid product. The product was recrystallized from aqueous ethanol to yield 19.2 g. of 1,2,3,4,4a,10b-hexahydro-(6H)- 1,4-methanodibenzo (c,e) 1,2 thiazine-S-oxide H o as a white, crystalline solid, M.P. 230-232 C. Elemental g analysis of this material showed 67.0% c, 6.54% H, I I and 5.98% N; calculated for the compound named, g 67.0% c, 6.49% H, 6.01% N. Infrared spectra were consistent with the structure of the named compound. The addition reaction is accomplished merely by con- 10 Example 2 tacting the two reactants at a temperature above about Z-N-sulfinylaminobiphenyl was prepared by the con- 50 C. Preferably, the reaction is carried out in inert ventional reaction of Z-aminobiphenyl with thionyl solvent solution at about 50-300 C. While the ratio of chloride in refluxing benzene. Using the procedure of reactants is not critical to success, best results are usually Example 1, 10.75 g. of 2-N-sulfinylaminobiphenyl and obtained when at least about one mole of the olefin is 4.7 g. of norbornene were combined in 200 ml. of toluene employed per mole of sulfinylaniline. Conveniently, the and the mixture was heated at reflux temperature for reaction is run at the reflux temperature of a solvent such 96 hours. The solids which separated from the cooled as toluene or xylene in which the reaction product is only reaction mixture were collected by filtration and recrysslightly soluble and so is largely precipitated from the tallized from methylcyclohexane to yield 9.4 g. of 1,2,3,4, reaction mixture upon cooling. Product separation is there- Y -P Y an i Z0(C, by simplified and optimum yields are obtainable. (1,2)thiazine-5-oxide as white needles melting at 187- Example 1 l89 C. The structurewas confirmed by elemental analy- SIS and infrared examination. I In a reaction flask equipped W1th a stlrrer, a m ogen Various substituted N-sulfinylanilines were prepared by mlet and a reflux condenser vented through a calcium reacting the substituted aniline with thionyl chloride. chloride drying tube, 1?.9 g. of N-sulfinylaniline and 9.4 g. These products were then reacted with norbornene by the of norbornene were dissolved in 300 ml. of toluene. The procedure of Example 1 to obtain the expected hexa reaction mixture was heated to its reflux temperature and hydrodibenzothiazines. In addition, S-cyanonorbornene was maintained at this temperature for 72 hours under was reacted with N-sulfinylaniline to obtain the cyanoa blanket of nitrogen. During the course of the reaction, substituted product. These results are summarized in the the mixture became dark and solids formed around the table which follows. Equal molar proportions of reactants stirrer blade and the thermometer well. The reaction were used except as noted. Yields in all examples are mixture was chilled in an ice bath and filtered to separate based on the amount of starting sulfinylaniline.

Examples 3-7 Reactants Product Meltiiglg Percent N-sulfinylaniline Norbornene Pomt G' Yleld 0 g p-Nitro- Norbornene..- l 260.5d 42,5

I NO:

0 g p-Methyl- Norbomene 211-214 (L... 20.2

0 g p-Methoxy Norbornene.. 188-190 10.6

o-ona See footnote at end of table.

. 'Examples 3-7-Continued Reaetants Product Melting Percent Point,"C. Yield N-sulfinylaniline Norbornene r t p-Ohloro- Norbornene- 196196.5d 7a l Cl 0 II Unsubstituted. -eyano- NH 259-260 d-. 7.7

borbornene.

(mixed 2 and 3 isomers) I 1 Yield was increased to 60% based on the sulfinylaniline by using a /1 molar excess of norbornene.

Example 8 To a reaction flask there was added 15.5 g. of 1,2,3,- 4,4a,10b hexahydro (6H) 9 nitro 1,4 methanodibenzo(c,e)-(1,2)thiazine-5-oxide (from the reaction of norbornene with p-nitro-N-sulfinylaniline), 1.55 g. of glacial acetic acid, 62 g. of iron filings, 186 g. of ethyl alcohol, and 93 ml. of Water. This mixture was stirred for '6 hours at its reflux temperature. The reaction mixture was filtered hot, the filtrate was made alkaline by addition of solid potassium carbonate, and filtered again. Evaporation of the solvent from the filtrate yielded 11 g. of a tan solid. The recrystallized product was cream colored needles, melting at 198-200 C. with some decomposition. Elemental and infrared analysis showed this compound to be 9-amino-1,2,3,4,4a,10b-hexahydro-(6H)- 1,4-methano-dibenz0 (c,e) (1,2)-thiazine-5-oxide.

Example 9 To a solution of 2.33 g. of the product of Example 1 and 0.6 g. of NaOH in aqueous tetrahydrofuran there was added 1.8 g. of dimethyl sulfate. This solution was heated and stirred for one hour. The solution was diluted with water and cooled to cause precipitation of unreacted starting material. The filtrate from the cooled solution was evaporated under reduced pressure to obtain a residue which upon recrystallization from methylcyclohexane gave colorless needles, M.P. 140-142 C. Infrared and elemental analysis showed this material to be the N- methylated compound, 1,2,3,4,4a,10b -hexahydro-(6H)- G-methyl-1,4-methanodibenzo (c,e) (1,2 thiazine-S-oxide.

By the general procedure of Examples 1-8 N-sulfinylaniline and substituted N-sulfinylanilines as shown above are reacted with methyl-substituted norbornenes as previously described to obtain the corresponding dibenzothiazines. Bornylene being a readily available methylated reactant, its reaction products are of particular interest.

These products have the structurewhere R is a radical as defined above. These products are alkylated as shown in Example 9 to give the N-alkyl compound. Where R is nitro, this is reducible to an amino group as shown in Example 8. These compounds derived from bornylene and other methylated norbornenes have properties closely similar to those of the compounds prepared in the above examples.

The compounds of this invention are useful for the control of parasitic worms in animals. Mice which were infected with such parasites as mouse tapeworms and mouse trichostrongylid larvae were found to be substantially free of these worms after having been fed for several days with a diet containing 0.06% by weight of one or more of these compounds.

These compounds are also useful as chemical intermediates for the preparation of new bridged carbazoles. The preparation of these carbazoles also serves as a confirmatory proof of structure for the dibenzothiazines described above. It has been found that. by reacting such dibenzothiazines with Raney nickel or equivalent desulfuri'zing reducing catalyst containing adsorbed hydrogen such as Raney cobalt in a lower alkanol, a bridged hexahydrocarbazole is produced according to the following reaction:

7 In the above equation, R represents a group as previously defined and A is lower alkyl. The reaction is carried out by contacting the reactants at moderate temperatures, using an excess of the nickel catalyst. Example 10 is illustrative.

Example 10 A mixture of 27 g. of l,2,3,4,4a,10b-hexahydro-1,4- methano-(6H)-dibenzo(c,e)(1,2)thiazine-5-oxide, 520 g. of Wet Raney nickel (65% Ni), and 500 ml. of ethyl alcohol was stirred at its reflux temperature for 26 hours. The nickel was then removed by filtration and the ethanol was evaporated under reduced pressure. Fractional distillation of the residual liquid yielded 17.3 g. of a viscous, colorless liquid, B.P. l66-170 C./ 14-15 mm. Hg. This material was identified by infrared spectroscopy and by nuclear magnetic resonance measurements as being 9-ethyl-1,2,3,4,4a,9a-hexahydro-1,4-methanocarbazole. The methyl iodide quaternary salt of this compound was prepared by the conventional method. The recrystallized methiodide obtained was found to melt at 165-166" C. Elemental analysis of this salt showed 54.3%, C, 6.74% H, 3.98% N; calculated for C H NI: 54.1% C, 6.25% H, 3.95% N.

By the method shown in Example 10, the substituted dibenzothiazines described in this specification are converted to the corresponding substituted N-alkylhexahydrom e thanocarbazoles. Substitution of methyl alcohol, propyl alcohol, or butyl alcohol for the ethyl alcohol shown in the above example yields the corresponding N-alkyl compound.

These carbazoles are useful contact insecticides, aqueous dispersions of 500 ppm. giving effective control of insects such as flies and cockroaches.

8 I claim: 1. A carbazole compound of the formula .N, RI

claim 1 which comprises reacting by contacting in lower alkanol solution a metal desulfurization reducing catalyst and a compound of the formula wherein R is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, phenyl, and nitro.

References Cited Sparatore: Ga'zz. Chim. Ital., vol. 88,- pp. 755-63 (1958).

Sparatore: Gazz. Chirn. Ital., vol. 92, pp. 596600 (1962).

WALTER A. MODAN-CE, Primary Examiner.

I. M. FORD, Assistant Examiner. 

1. A CARBAZOLE COMPOUND OF THE FORMULA 